Huntington disease (HD) is an adult-onset neurodegenerative disease caused by a CAG expansion in the HTT gene. HD is characterized by striatal atrophy and is associated with motor, cognitive and psychiatric deficits. In the presence of the HD mutation, the interactions between huntingtin (HTT) and huntingtin interacting protein 14 (HIP14 or DHHC17) and HIP14-like (DHHC13, a HIP14 orthologue), palmitoyl acyltransferases for HTT, are disturbed, resulting in reduced palmitoylation of HTT. Genetic ablation of either Hip14 or Hip14l recapitulates many features of HD, including striatal atrophy and motor deficits. However, there are no changes in palmitoylation of HTT in either mouse model and, subsequently, the similarities between the phenotypes of these two mouse models and the HD mouse model are believed to result from underpalmitoylation of other HIP14 and HIP14L substrates. HTT acts as a modulator of HIP14 activity such that in the presence of the HD mutation, HIP14 is less active. Consequently, HIP14 substrates are less palmitoylated, leading to neuronal toxicity. This suggests that altered HIP14–HTT and HIP14L–HTT interactions in the presence of the HD mutation reduces palmitoylation and promotes mislocalization of HTT and other HIP14/HIP14L substrates. Ultimately, HD may be, in part, a disease of altered palmitoylation.
Skip Nav Destination
Article navigation
April 2015
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Conference Article|
April 07 2015
Aberrant palmitoylation in Huntington disease
Shaun S. Sanders;
Shaun S. Sanders
1
*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada
1To whom correspondence should be addressed (emailssanders@cmmt.ubc.ca).
Search for other works by this author on:
Michael R. Hayden
Michael R. Hayden
*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 08 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem Soc Trans (2015) 43 (2): 205–210.
Article history
Received:
September 08 2014
Citation
Shaun S. Sanders, Michael R. Hayden; Aberrant palmitoylation in Huntington disease. Biochem Soc Trans 1 April 2015; 43 (2): 205–210. doi: https://doi.org/10.1042/BST20140242
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.